<p>Colorectal cancer (CRC) is a relatively widespread malignancy that contributes to considerable mortality and healthcare challenges. Recent studies emphasize the significance of N6-methyladenosine (m⁶A) RNA modification in CRC progression. However, research on KIAA1429 (a key m⁶A methyltransferase) is still limited during CRC. This study focuses on investigating the impact of KIAA1429-driven m⁶A modification on CRC progression.&#xa0;The expression of KIAA1429 in CRC was assessed via bioinformatics analyses and qRT-PCR methods. Its impact on CRC cell malignancy was examined by employing CCK8, colony formation, wound healing, and transwell invasion assays. The relationship among KIAA1429 and Family with sequence similarity 84, member B (FAM84B) was verified via qRT-PCR, immunoblotting, and MeRIP. Finally, the effect of their interaction on CRC cell malignancy and Wnt/β-catenin signaling was assessed in vitro and in vivo.&#xa0;The KIAA1429 expression was markedly high in CRC, and silencing it significantly reduced malignant phenotypes of CRC cells. The bioinformatics analysis identified FAM84B as a target gene of KIAA1429 in CRC, with elevated expression and m⁶A-dependent methylation regulation by KIAA1429. The outcomes of qRT-PCR, immunoblotting and MeRIP assay confirmed a positive association between KIAA1429 and FAM84B. Furthermore, KIAA1429 silencing partially decreased β-catenin levels and reversed the malignant effects of FAM84B overexpression on CRC cells, both in vitro and in vivo.&#xa0;The results illustrate that KIAA1429 promotes CRC tumorigenesis by stabilizing FAM84B mRNA and activating the Wnt/β-catenin pathway, highlighting its capability as a prognostic biomarker and therapeutic target for CRC.</p> Graphical Abstract <p></p>